The actions of glucagon, vasopressin and yield-adrenergic agents on perfused liver and isolated livercells cause modifications of the mitochondrial adenine nucleotide pool and the electron transport chain. These effects persist after isolation of the mitochondria. The proposal aims to investigate the mechanisms by which the different hormones exert their effects and the physiological consequences thereof. Glucagon, phenylephrine and vasopressin exert their effects via different messenger signals; yet, they show similar effects on the mitochondrial characteristics in a steady state. The effect of these hormones will be studied during the initial phase of the reaction and after disruption of the plasma membrane with digitonin Variation of the redox state of NAD(P), the substrate supply, the availability of Ca2+ and the interference of insulin with their activity will be used to study different potential modes of action, e.g., involving changing mitochondrial substrate fluxes or through Ca-calmodulin dependent, protein kinase dependent, glutathione dependent mechanisms. The study of the physiological significance of these effects will concentrate on the hypothesis that the activity of the adenine nucleotide translocator is a potential site of control for hormone action, which relates intra- and extra-mitochondrial ATP-utilizing reactions to the phosphorylation potential in mitochondria and cytosol. These parameters will be studied in relation to the mitochondrial membrane potential and pH difference, both after short-term hormone treatment and in diabetes.